Computational electrophysiology: The molecular dynamics of ion channel permeation and selectivity in atomistic detail

C. Kutzner, H. Grubmüller, B.L. De Groot, Ulrich Zachariae

    Research output: Contribution to journalArticlepeer-review

    118 Citations (Scopus)

    Abstract

    Presently, most simulations of ion channel function rely upon nonatomistic Brownian dynamics calculations, indirect interpretation of energy maps, or application of external electric fields. We present a computational method to directly simulate ion flux through membrane channels based on biologically realistic electrochemical gradients. In close analogy to single-channel electrophysiology, physiologically and experimentally relevant timescales are achieved. We apply our method to the bacterial channel PorB from pathogenic Neisseria meningitidis, which, during Neisserial infection, inserts into the mitochondrial membrane of target cells and elicits apoptosis by dissipating the membrane potential. We show that our method accurately predicts ion conductance and selectivity and elucidates ion conduction mechanisms in great detail. Handles for overcoming channel-related antibiotic resistance are identified.
    Original languageEnglish
    Pages (from-to)809-817
    Number of pages9
    JournalBiophysical Journal
    Volume101
    Issue number4
    DOIs
    Publication statusPublished - 17 Aug 2011

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